Developmental neuromuscular synapse elimination: Activity-dependence and potential downstream effector mechanisms

Synaptic connections initially formed during nervous system development undergo a significant transformation during nervous system maturation. Such maturation is essential for the proper architecture and function of the nervous system. Developmental synaptic transformation includes synapse elimination, a process in which multiple immature presynaptic inputs converge at and compete for control of a common postsynaptic target. This developmental synaptic remodeling is best understood at mammalian neuromuscular junctions. It is well established that neuromuscular activity provides the impetus for the pruning of redundant motor axon inputs. Despite the dominant influence neuromuscular activity exerts on developmental synapse elimination, however, the downstream mechanisms of neuromuscular activity that affect synapse elimination remain poorly understood. Conversely, although several cellular and molecular effector mechanisms are known to impact synapse elimination, it is unclear whether they are modulated by neuromuscular activity. This review discusses how the motor neurons, synaptic glia and muscle fibers each contributes to the developmental phenomenon, and speculates how neuromuscular activity may modulate these contributions.